Noll, T. (Corresponding author)

1999
Forschungszentrum, Zentralbibliothek Jülich

Report No.: Juel-3658

Abstract: This study presents the development of a continuously operating fluidized-bed bioreactor for on-line evaluation of radiotracers in vitro, which combines tissue-like three-dimensional cell cultivation in open porous microcarriers with a technique for on-line radioactivity detection. The long time stability of steady-state permits a large number of experiments using the same culture. All relevant parameters (02, pH, T, etc.) can be adjusted according to the experimental requirements. The flux of the circulating medium can be adapted to the blood flow of the corresponding organism, while the input function of the radiotracer is freely adjustable for simulation of in vivo conditions. Sampling and examination of the immobilized cells are possible at any time. Using this system, the kinetics of 2-[18F]f1uoro-2-deoxyglucose (FDG) in human glioma cells (86HG39) were studied and it was shown that the dependence of the lumped constant (LC) for FOG on the medium glucose concentration is similar to that obtained in the rat brain. For normoglycemic concentrations the LC was determined to be in the range of 0.7, while in hypoglycemia it increased progressively up to a value of 1.22 at a glucose concentration of 3 mM. The rate constants in the three compartment model were found to be similar to those obtained in vivo using PET; indicating the validity of the system for tracer evaluation. Furthermore the kinetics of both diastereomeric forms of 4-[18F]f1uoro-proline was investigated and found that both diastereomeres were not metabolized and reached an identical intracellular steady state concentration. The trans-form was transported three times faster than the the cis-diastereomere, indicated by the rate constants.

Keyword(s): bioreactor ; fluidized bed reactor ; tracer technique ; radiopharmaceutical ; immobilized cell ; cell culture

1. Institut für Biotechnologie (IBT)